The protective efficacy of immune globulin (IG) in the prevention of hepatitis C virus (HCV) infection is unknown. There have been conflicting reports in the literature regarding the ability of IG to prevent or modify post-transfusion HCV infection. We studied experimentally infected chimpanzees in order to assess the potential value of IG and an anti-HCV enriched IG preparation (HCIG) in a post- exposure setting. HCIG was prepared by standard Cohn-Oncley fractionation from a pool of 23 plasma samples that had high titers of anti-HCV. Cohn fraction II from this fractionation (consisting primarily of IgG) was formulated as a 5.4% solution in 0.1 M glycine at pH 4.0. Three male chimpanzees were each infected with 30 CID of HCV inoculum (US-1 strain). After approx. 30 min, one chimpanzee was treated with 35 ml of the HCIG preparation, one received the same quantity of an intravenous immune globulin (IGIV) that was anti-HCV negative, and one received no additional treatment. In the untreated and the IGIV- treated chimpanzees, acute hepatitis C developed with ALT peak on day 59 (10.8 and 15.0 times normal, respectively); anti-HCV (EIA 2.0, Abbott) was found in sera as early as day 42. In the chimpanzee treated with HCIG, however, acute hepatitis was markedly delayed. For the first 70 days after HCIG treatment, this chimpanzee was positive for anti-HCV and had minimal elevation of ALT (1.27 times normal). During the next 27 days, anti-HCV became negative and the ALT level increased (2.06 times normal). Anti- HCV occurred again on day 97 and acute hepatitis ensued with ALT peak (10.6 times normal) on day 146. Thus, postexposure HCIG treatment prolonged the incubation period of acute hepatitis C but did not prevent or delay HCV infection. Since the occurrence of acute hepatitis roughly coincided with the disappearance of anti-HCV in this animal, it appears possible that HCIG contained the spread of the infection in the liver and delayed clinical and pathological evidence of acute hepatitis. Standard IGIV had no effect on the course of HCV infection.